期刊
ARCHIVES OF TOXICOLOGY
卷 89, 期 1, 页码 73-85出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s00204-014-1238-2
关键词
Rho-kinase (ROCK); Inflammasome; Carbon nanotube; Asbestos; THP-1 cell
类别
资金
- JSPS KAKENHI [24590868]
- Grants-in-Aid for Scientific Research [24590868] Funding Source: KAKEN
Long fibers, such as asbestos and carbon nanotubes (CNTs), are more potent activators of inflammatory and genotoxicity than short or tangled fibers. Fibrous particles trigger interleukin (IL)-1 beta secretion and cause inflammatory diseases through NLRP3 inflammasomes in phagocytotic cells. However, the mechanism involved in fibrous particle-induced inflammation has not been well documented. In this study, we focused on GTPase effector Rho-kinases (ROCK1, and 2), which are known to be involved in a wide range of cellular functions such as adhesion, regulation of cytoskeleton, and phagocytosis. We examined whether ROCKs are associated with multi-walled CNT (MWCNT)- or asbestos-induced IL-1 beta secretion in human monocytic THP-1 cells using a selective inhibitor and small interfering RNA. THP-1 cells were differentiated to macrophages by PMA and were exposed to MWCNTs, crocidolite asbestos or lipopolysaccharide (LPS) in the presence or absence of Y27632 (ROCK inhibitor) or Z-YVAD (caspase-1 inhibitor). Exposure of the cells to MWCNTs or asbestos provoked IL-1 beta secretion, but this secretion was suppressed by both Y27632 and Z-YVAD, whereas LPS-induced IL-1 beta secretion was inhibited only by Z-YVAD and not by Y27632. siRNA designed for knockdown of both ROCK1 and ROCK2 suppressed MWCNT- and asbestos-induced IL-1 beta secretion, but did not change LPS-induced IL-1 beta secretion. Moreover, Y27632 suppressed pro-IL-1 beta protein levels and the release of activated-cathepsin B and activated-caspase-1 induced by MWCNTs or asbestos. In contrast, LPS-induced pro-IL-1 beta protein was not suppressed by Y27632. These results suggest that ROCKs are involved in fibrous particle-induced inflammasome responses in THP-1 cells.
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